title: Methods to determine mechanism of action of anti-influenza inhibitors.
abstract: Mechanism of action studies can be used to demonstrate an inhibitor's ability to specifically inhibit viral replication via a virus-specific or host cell target. A well-characterized mechanism of action is useful in evaluating potential off-target toxicities (e.g., a viral polymerase inhibitor may be assessed for inhibition of host polymerase) and in designing studies to monitor the development of resistance. Several methods can be used to elucidate the mechanism of action of an anti-influenza inhibitor. The first group of methods establishes that the activity of an inhibitor occurs at concentrations that do not cause cytotoxicity, investigates the selective inhibition of influenza, and indicates that inhibition is virus specific in nature. The second group of methods establishes the site of action, typically a target protein, and includes genotypic and phenotypic analysis of variants selected under inhibitor pressure. Finally, methods for measuring virion associated activities and their inhibition are described.
authors.affiliation: Biota Pharmaceuticals, Inc., Notting Hill, VIC, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Luttick
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hamilton
authors.forename: Simon P
authors.initials: SP
authors.lastname: Tucker
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002470:Cell Survival; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects / Q000502:physiology; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D060005:Genotyping Techniques; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology*; D008826:Microbial Sensitivity Tests / Q000379:methods; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D014771:Virion / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase